Soluplus Stabilized Amorphous Dispersions for Enhanced Oral Absorption of Felodipine

Background: Overcoming the poor aqueous solubility of small-molecule drugs is a major challenge in developing clinical pharmaceuticals. Felodipine (FLDP), an L-type calcium calcium channel blocker, is a poorly water-soluble drug.

Objectives: The study aimed to explore the potential applications of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) stabilized amorphous dispersions for augmenting the oral delivery of poorly water-soluble drugs.

Methods: Soluplus-stabilized amorphous FLDP (FLDP-SSAs) was prepared using a two-phase mixing method. The samples were analyzed for their microscopic and macroscopic behavior using polarized light microscopy (PLM), differential scanning calorimetry (DSC), molecular simulation, and in vitro dissolution studies. Subsequently, the pharmacokinetics of FLDP-SSAs were evaluated.

Results: The maximum drug-to-Soluplus mass ratio of FLDP-SSAs was 50:50, with a drug concentration of 8.0 mg/mL. They exhibited an amorphous nature, as confirmed by PLM and DSC. FLDPSSAs generated nanoparticles with a particle size of approximately 50 nm during in vitro dissolution. Compared to FLDP oral solution, FLDP-SSAs exhibited higher solubility due to their amorphous nature and the generation of nanoparticles. The area under the curve (AUC) for oral FLDP-SSAs was 16.7-fold larger than that of the FLDP suspension.

Conclusion: FLDP-SSAs could stabilize FLDP in an amorphous state and serve as drug carriers to enhance oral absorption.